Variations in the physiological levels of glucose, lactate O2 and CO2 can provide an early indication of metabolic abnormalities that are usually progressive with weight gain associated with obesity. Although a number of metabolic trends related to obesity have been established, exact metabolite interrelationships and complexities as they pertain to obesity progression and the development of associated diseases are less well defined. In addition, obesity and associated metabolic changes appear to be patient-specific and this is largely uninvestigated. Metabolite imbalance resulting from obesity is known to lead to the development of a number of serious diseases including diabetes, cardiovascular diseases, cancer and respiratory depression. Over the past 5 years our team has been researching a revolutionary, totally implantable biosensor platform capable of continuously monitoring glucose. This miniaturized (0.5 x 0.5 x 5 mm) sensor platform is inserted subcutaneously through a needle and operated remotely through a personal digital assistant (PDA) device. One of the key components of this sensor platform is its coating, which is capable of controlling the tissue/implant interface by suppressing inflammation, fibrous encapsulation and inducing neo-angiogenesis. The proposed research intends to make a quantum-advance in metabolic monitoring by allowing simultaneous sensing of multiple analytes (i.e. glucose, lactate O2 and CO2). The trends of these analytes under various biological conditions (i.e. fed, fasting and light exercise) for normal and obese rats will be established for comparison with our proposed multi-analyte sensor. The close proximity of the four electrochemical sensors requires additional advances in device integration. By the end of the proposed three-year study, a first generation multi-analyte sensor will be realized along with coating optimization to permit one month in vivo operation. This sensor is envisioned to achieve a quantum leap in metabolic monitoring and will provide researchers in the field with the means to investigate the complexities of obesity and associated disease states. The small size and low cost will increase patient acceptance and compliance and will allow monitoring of large numbers of patients in a normal home environment and for extended periods of time. Such data will be extremely valuable to researchers in the field to assist in understanding the complexities and patient-specific nature of obesity. Moreover, we envision future integration of this multi-analyte sensory platform to provide closed-loop insulin/glucagon delivery for tight control of glucose levels in diabetic patients. [unreadable] [unreadable] [unreadable] [unreadable]